NIR response type biomimetic membrane nano vesicle as well as construction method and application thereof

A technology of nanovesicles and construction methods, which can be applied to pharmaceutical formulations, preparations for in vivo experiments, medical preparations with non-active ingredients, etc., and can solve problems such as T cell exhaustion and the inability to exert cytotoxic T cell immune response effects , to inhibit the growth of

Active Publication Date: 2021-10-29
THE UNIV OF HONG KONG SHENZHEN HOSPITAL +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] studies have found that TILs are often confined to the stromal region of the tumor microenvironment rather than around tumor cells, in which tumor-associated fibroblasts (Cancer-associated fibroblasts, CAFs) pass through Activation of PD-L2 and FASL depletes CD8+ T cells and prevents the immune response of cytotoxic T cells

Method used

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  • NIR response type biomimetic membrane nano vesicle as well as construction method and application thereof
  • NIR response type biomimetic membrane nano vesicle as well as construction method and application thereof
  • NIR response type biomimetic membrane nano vesicle as well as construction method and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0079] 1) Preparation of an IR-780 iodide-modified lipid graft (IR780-PEG2000-DSPE)

[0080] The IR-780 iodide-modified lipid graft (IR780-PEG2000-DSPE) provided in Example 1 is synthesized by a substitution method, which specifically includes the following steps:

[0081] Weigh 10mg of IR-780 iodide and 40mg of NH 2 -PEG2000-DSPE, accurately weighed, dissolved in dichloromethane solution to obtain a dichloromethane solution containing IR-780 iodide; with triethylamine (TEA) as the acid-binding agent, triethylamine (TEA) and The molar ratio of IR-780 iodide is 2: 1 ratio and weighs triethylamine (TEA), and adds in the described dichloromethane solution that contains IR-780 iodide, room temperature stirring reaction 24h; After the reaction finishes, Add the reaction solution to 10 times the volume of anhydrous ether, overnight at 4°C, then centrifuge at 3000 rpm for 5 minutes to remove by-products, and then dry the precipitate to obtain IR-780 iodide-modified lipids Graft (IR...

Embodiment 2

[0094] 1) Preparation of an IR-780 iodide-modified lipid graft (IR780-PEG2000-DSPE)

[0095] The preparation method of the IR-780 iodide-modified lipid graft (IR780-PEG-2000-DSPE) provided in Example 2 is the same as that in Example 1, and no further description is made here.

[0096] 2) About the construction of a thermosensitive lipid drug delivery system

[0097] The thermosensitive lipid drug delivery system provided in Example 2 is constructed through the following steps:

[0098] Taking the inhibitor BMS202 (BMS) as a model drug, weigh the IR-780 iodide-modified lipid graft (IR780-PEG2000-DSPE) obtained in the inhibitor BMS202, Example 1, thermosensitive lipid DPPC and cholesterol respectively, and Dissolve the weighed inhibitor BMS202, IR-780 iodide-modified lipid graft (IR780-PEG2000-DSPE), thermosensitive lipid DPPC and cholesterol in ethanol, and heat in a water bath at 60°C to obtain the ethanol phase Solution (in this solution, the mass percentage of inhibitor BM...

Embodiment 3

[0105] 1) Preparation of an IR-780 iodide-modified lipid graft (IR780-PEG2000-DSPE)

[0106] The preparation method of the IR-780 iodide-modified lipid graft (IR780-PEG2000-DSPE) provided in Example 3 is the same as that in Example 1 and will not be described here.

[0107] 2) About the construction of a thermosensitive lipid drug delivery system

[0108] The thermosensitive lipid drug delivery system provided in Example 3 is prepared through the following steps:

[0109] Taking the inhibitor BMS202 (BMS) as a model drug, weigh the IR-780 iodide-modified lipid graft (IR780-PEG2000-DSPE) obtained in the inhibitor BMS202, Example 1, thermosensitive lipid DPPC and cholesterol respectively, and Dissolve the weighed inhibitor BMS202, IR-780 iodide-modified lipid graft (IR780-PEG2000-DSPE), thermosensitive lipid DPPC and cholesterol in ethanol, and heat in a water bath at 60°C to obtain the ethanol phase Solution (in this solution, the mass percentage of inhibitor BMS202 is 20%, t...

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Abstract

The invention discloses an NIR response type biomimetic membrane nano vesicle and a construction method and application thereof. The construction method comprises the following steps of S1, collecting tumor cells, and obtaining a tumor cell membrane solution through a freeze thawing method, gradient centrifugation and resuspension in sequence; S2, adopting a solvent diffusion method to obtain a thermosensitive lipid drug delivery system; and S3, mixing the tumor cell membrane solution with a thermosensitive lipid drug delivery system, and performing extruding and filtering by using a liposome extruder to obtain the NIR response type biomimetic membrane nano vesicle. The NIR response type biomimetic cell membrane nano vesicle prepared by the method provided by the invention has a tumor efficient homologous targeting function, further blocks a PD-1/PD-L1 pathway, reverses a tumor immunosuppression state for a long time, synergistically exerts anti-tumor immune response, and inhibits growth of primary tumors and metastases.

Description

technical field [0001] The invention belongs to the technical field of biopharmaceuticals, and in particular relates to a NIR-responsive biomimetic membrane nanovesicle and its construction method and application. Background technique [0002] Tumor immunotherapy is to activate the body's immune system by introducing a functional antigen-specific immune response to achieve long-term immune memory, prevention and killing of tumor cells. However, currently about 85% of tumor patients do not respond well to immunotherapy. Studies have found that the tumor microenvironment can protect tumor cells and perform immune escape through mechanisms such as immunosuppression. [0003] Immune checkpoint blockade (ICB) therapy, which reverses the tumor immunosuppressive tumor microenvironment (TME), has become the main way of immunotherapy. Among them, ICB therapy targeting the PD-1 / PD-L1 pathway has shown significant clinical efficacy in various types of cancers such as melanoma, non-sma...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/127A61K41/00A61K45/00A61K47/46A61K49/00A61P35/00A61P35/04
CPCA61K41/0052A61K41/0028A61K9/1271A61K9/1277A61K47/46A61K45/00A61P35/00A61P35/04A61K49/0021A61K49/0084
Inventor 谭亚南关新元李咏梅李珊珊罗敏
Owner THE UNIV OF HONG KONG SHENZHEN HOSPITAL
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